Pericyte-Assisted Vascular Lumen Organization in a Novel Dynamic Human Blood-Brain Barrier-on-Chip Model

Area of Science:

• Neuroscience
• Biomedical Engineering
• Cell Biology

Background:

• Organ-on-Chip (OoC) technology offers advanced in vitro models for studying complex biological systems.
• The blood-brain barrier (BBB) is critical for brain function, and its microenvironment is challenging to replicate.
• Understanding neurovascular unit mechanobiology requires models that incorporate dynamic flow and cellular interactions.

Purpose of the Study:

• To develop and utilize a novel microfluidic device to mimic brain microcirculation.
• To investigate the morphological and structural adaptations of human brain endothelial cells (ECs) under pulsatile flow.
• To determine the role of pericytes and astrocytes in modulating EC responses within the BBB model.

Main Methods:

• A microfluidic device with square microchannels was engineered to simulate brain microvessels.
• Human brain ECs were cultured and subjected to pulsatile flow in co-culture with pericytes and astrocytes.
• Cell morphology, cytoskeletal organization, and barrier properties were analyzed under varying conditions.

Main Results:

• Pulsatile flow significantly influenced brain EC morphology and cytoskeletal organization.
• In the absence of perivascular cells, ECs showed a stretched morphology with prominent actin stress fibers.
• Co-culture with pericytes and astrocytes led to endothelial rearrangement, lumen formation, and improved barrier function.

Conclusions:

• Perivascular cells play a vital role in regulating endothelial cell responses to mechanical forces in the neurovasculature.
• The developed OoC model provides valuable insights into BBB mechanobiology and neurovascular unit function.
• This technology advances in vitro modeling for drug discovery and disease research related to the brain.